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Centre for Misfolding Diseases

Educational background

I completed my BSc in Biochemistry at the Lebanese University during which I became interested in understanding the protein folding process. In order to pursue my interests, I joined an MSc programme in Aix-Marseille University, France, where I studied the folding of unstructured proteins, namely intrinsically disordered proteins.

My research during my MSc and PhD was centred on understanding the molecular mechanisms by which the folding of disordered proteins upon binding to their partners results in the gain of a function, which leads in some cases to human diseases. In particular, I studied the role of intrinsically disordered proteins in orchestrating the replicative machinery of RNA virsues.

Current research

After my PhD, I joined the Centre for Misfolding Diseases, where my research to date mainly focuses on the generation of new methods that allow the detailed understanding of the molecular principles underlying the misfolding of intrinsically disordered proteins, a hallmark of many diseases, such as Alzheimer’s and Parkinson’s diseases, for the aim of drug discovery.

At the Centre, I have worked on elucidating the fundamental principles of protein aggregation and on developing quantitative tools for the assessment of the efficacy of drug molecules in modulating the protein aggregation process. In collaboration with many colleagues and based on the accumulated knowledge in the Centre, we have set up an innovative and interdisciplinary drug discovery programme that aims at the selective targeting of specific microscopic processes in a controlled intervention during the aggregation of proteins associated with misfolding diseases, in particular Alzheimer’s and Parkinson’s diseases. A direct consequence of this endeavour was the ability to reach, for the first time, a detailed understanding of the mode of action of drug molecules on single microscopic steps during the aggregation process.

Research translation

This contribution has led to the translation of the drug discovery programme into practice by creating Wren Therapeutics, a biopharmaceutical company, in which I am currently the Head of R&D. Wren Therapeutics aims at bridging the gap between fundamental and translational research in order to generate transformative treatments across a wide range of protein misfolding diseases.

Publications

Rational design of a conformation-specific antibody for the quantification of Aβ oligomers
FA Aprile, P Sormanni, M Podpolny, S Chhangur, L-M Needham, FS Ruggeri, M Perni, R Limbocker, GT Heller, T Sneideris, T Scheidt, B Mannini, J Habchi, SF Lee, PC Salinas, TPJ Knowles, CM Dobson, M Vendruscolo
– Proceedings of the National Academy of Sciences
(2020)
117,
13509
Complexity in Lipid Membrane Composition Induces Resilience to Aβ42 Aggregation
M Sanguanini, KN Baumann, S Preet, S Chia, J Habchi, TPJ Knowles, M Vendruscolo
– ACS Chem Neurosci
(2020)
11,
1347
Transthyretin Inhibits Primary and Secondary Nucleations of Amyloid-β Peptide Aggregation and Reduces the Toxicity of Its Oligomers
SA Ghadami, S Chia, FS Ruggeri, G Meisl, F Bemporad, J Habchi, R Cascella, CM Dobson, M Vendruscolo, TPJ Knowles, F Chiti
– Biomacromolecules
(2020)
21,
1112
Trodusquemine enhances Aβ 42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes
R Limbocker, S Chia, FS Ruggeri, M Perni, R Cascella, GT Heller, G Meisl, B Mannini, J Habchi, TCT Michaels, PK Challa, M Ahn, ST Casford, N Fernando, CK Xu, ND Kloss, SIA Cohen, JR Kumita, C Cecchi, M Zasloff, S Linse, TPJ Knowles, F Chiti, M Vendruscolo, CM Dobson
– Nature Communications
(2019)
10,
225
Bacterial production and direct functional screening of expanded molecular libraries for discovering inhibitors of protein aggregation.
DC Delivoria, S Chia, J Habchi, M Perni, I Matis, N Papaevgeniou, M Reczko, N Chondrogianni, CM Dobson, M Vendruscolo, G Skretas
– Science Advances
(2019)
5,
eaax5108
Chemical and mechanistic analysis of photodynamic inhibition of Alzheimer's β-amyloid aggregation
M Ahn, BI Lee, S Chia, J Habchi, JR Kumita, M Vendruscolo, CM Dobson, CB Park
– Chemical communications (Cambridge, England)
(2019)
55,
1152
Stabilization and Characterization of Cytotoxic Aβ
B Mannini, J Habchi, S Chia, FS Ruggeri, M Perni, TPJ Knowles, CM Dobson, M Vendruscolo
– ACS chemical neuroscience
(2018)
9,
2959
SAR by kinetics for drug discovery in protein misfolding diseases
S Chia, J Habchi, TCT Michaels, SIA Cohen, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo
– Proceedings of the National Academy of Sciences
(2018)
115,
10245
Microfluidic deposition for resolving single-molecule protein architecture and heterogeneity.
FS Ruggeri, J Charmet, T Kartanas, Q Peter, S Chia, J Habchi, CM Dobson, M Vendruscolo, TPJ Knowles
– Nature communications
(2018)
9,
3890
Structure-based design of allosteric calpain-1 inhibitors populating a novel bioactivity space.
L Kalash, J Cresser-Brown, J Habchi, C Morgan, DJ Miller, RC Glen, RK Allemann, A Bender
– European Journal of Medicinal Chemistry
(2018)
157,
1264
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Research Staff Scientist

Telephone number

01223 336427 (shared)

Email address